Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000693471 | SCV000821342 | uncertain significance | Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 555 of the SPATA5 protein (p.Ser555Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SPATA5-related conditions. ClinVar contains an entry for this variant (Variation ID: 572155). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SPATA5 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
3billion, |
RCV000693471 | SCV005329025 | uncertain significance | Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome | 2024-09-20 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.001%). Damaging effect on gene or gene product predicted by in silico programs is uncertain [REVEL: 0.13 (damaging >=0.6, benign <0.4), 3Cnet: 0.52 (damaging >=0.6, benign <0.15)]. Therefore, this variant was classified as uncertain significance. |